Immune senescence is a state of diminished immune competence manifested by reduced ability to respond to and clear pathogens and tumors, and it is believed to significantly contribute to morbidity and mortality in older individuals. Caloric restriction (CR) is the only intervention that consistently and significantly prolongs lifespan and delays the age-associated morbidity and mortality in experimental animals, but its mechanism of action is incompletely understood. CR appears to exert beneficial effects on the aging rodent immune system. However, it is not known whether CR can reverse immune senescence, or whether CR would similarly impact the immune system of primates. In this proposal, we shall elucidate the effects of aging upon the immune system of Rhesus Macaques, and test the hypothesis that CR acts to maintain T-cell subset balance and preserve T-cell responsiveness in aged Rhesus Macaques. To that ene, we shall measure key immunological parameters known to be affected by aging in other species. Cross-sectional studies will be performed in young and old animals fed regular or CR diets. Specific aims will examine the effects of aging and CR on T-cell subset frequencies and function (Aim 1), thymic output and peripheral T-cell homeostasis (Aim 2), TCR diversity of T-cell subsets (Aim 3), and T-cell subset gene expression patterns (Aim 4). These studies will comprehensively and precisely characterize the effects of aging and CR in a real-life, outbred primate model. This will not only test the validity of observations in rodents, but also put limits on current hypotheses and allow for the rational setting of new ones.